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Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel thiohydantoin derivatives as antiproliferative agents: A combined experimental and theoretical assessments

In our endeavors to develop potent anticancer agents, novel two series of 3,5-disubstituted-2-thiohydantoins 5a–c and the S-methyl counterparts 6a–c were designed and synthesized. The structural modifications were based on some reported thiohydantoins derivatives which showed promising antiproliferative activity. The activity of the compounds was verified via the in vitro cytotoxicity assay against prostate (PC-3) and breast (MCF-7) cancer cell lines along with normal lung fibroblast cell line (WI-38) to determine their safety on the normal cells. The tested compounds 5a–c and 6a–c showed promising cytotoxicity with IC50 ranges from 1.980 to 19.089 μM and from 1.619 to 16.976 μM against PC-3 and MCF-7, respectively. Interestingly, compound 6c is the most potent derivative against both PC-3 and MCF-7 (IC50 = 1.980 and 1.619 μM, respectively). Compound 5c is the second most potent derivative against PC-3 and MCF-7(IC50 = 2.385 and 2.084 μM, respectively). The antiproliferative activities on the normal lung fibroblast cell line (WI-38) implied that the most potent cytotoxic derivatives 5c and 6c are safe on the healthy cells. The docking solutions of 5c and 6c into the active site of TOP1 inferred comparable binding interactions to the co-crystallized ligand with docking scores = - 6.859 and 6.939 Kcal/mol, respectively. The computational studies using DFT calculations with B3LYP/6-31+G (d,p) level were performed to study the electronic and geometric properties obtained from the stable structure of the investigated compounds. A good correlation was found between the quantum chemical parameters and experimental observations. Therefore, these promising thiohydantoins can be subjected for further optimization to develop more potent counterparts.

Enantioselective Synthesis of 5,5-Disubstituted Hydantoins by Br?nsted Base/H-Bond Catalyst Assisted Michael Reactions of a Design Template

A new method for the enantioselective synthesis of 5,5-disubstituted (quaternary) hydantoins was developed on the basis of an organocatalytic Michael reaction approach involving the use of 2-benzylthio-3,5-dihydroimidazol-4-ones as key hydantoin surrogates. The method is general with respect to the substitution pattern at the hydantoin N1 (alkyl, aryl, acyl), N3 (aryl), and C5 (linear/branched alkyl, aryl) positions and affords essentially single diastereomeric products with enantioselectivities higher than 95 % ee in most cases. Among the bifunctional Br?nsted base/H-bond catalysts examined, a known squaramide–tertiary amine catalyst and a newly prepared squaramide–tertiary amine catalyst provide the highest selectivity so far with either nitroolefins or vinyl ketones as the acceptor components. Kinetic measurements support a first-order rate dependence on both reaction partners, the donor template and the Michael acceptor, whereas competitive 1H NMR spectroscopy experiments reveal the high ability of the template for catalyst binding.

Microwave-assisted solid-state synthesis and characterization of thiohydantoin derivatives

A new and efficient solid-state method for the preparation of thiohydantoins is reported. With this method, twelve thiohydantoin compounds have been synthesized in good to excellent yields (81-92%). In addition, this method has the advantages of high yields, a cleaner reaction, simple methodology, and short reaction times. Copyright Taylor & Francis, Inc.